7-101172387-C-A

Variant names:

• chr7-101172387-C-A
• NM_198571.3:c.802G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198571.3(NAT16):​c.802G>T​(p.Val268Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAT16 NM_198571.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.673

Genes affected

NAT16 (HGNC:22030): (N-acetyltransferase 16 (putative)) Predicted to enable acyltransferase activity, transferring groups other than amino-acyl groups. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072543174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT16	NM_198571.3	c.802G>T	p.Val268Leu	missense_variant	Exon 4 of 4	ENST00000300303.7	NP_940973.2
NAT16	NM_001369694.1	c.802G>T	p.Val268Leu	missense_variant	Exon 5 of 5		NP_001356623.1
NAT16	NM_001369695.1	c.802G>T	p.Val268Leu	missense_variant	Exon 4 of 4		NP_001356624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT16	ENST00000300303.7	c.802G>T	p.Val268Leu	missense_variant	Exon 4 of 4	2	NM_198571.3	ENSP00000300303.2
NAT16	ENST00000455377.5	c.802G>T	p.Val268Leu	missense_variant	Exon 5 of 5	1		ENSP00000395125.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.802G>T (p.V268L) alteration is located in exon 4 (coding exon 3) of the NAT16 gene. This alteration results from a G to T substitution at nucleotide position 802, causing the valine (V) at amino acid position 268 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0088	T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.47	.;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.068
Sift	Benign	0.41	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.021	B;B
Vest4		0.12
MutPred		0.27		Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.067
MPC		0.50
ClinPred		0.25	T
GERP RS		-0.0058
Varity_R		0.11
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-100815668;